Pharmacology Flashcards
What is the mechanism of penicillin?
Binds to penicillin binding proteins and inhibits transpeptidase rxn and cross linking of peptidoglycans
What are some adverse effects of penicillin?
hypersensitivity: hives, shortness of breath, anaphylactic shock, or mild-rash
diarrhea
superinfections
What bacteria are sensitive to Penicillin G?
Streptococci and meningococci. Gram negative bacteria’s outer membrane limits entry of drug.
What are examples of antibiotics to treat penicillinase resistant staphylococci? (excluding MRSA)
Nafcillin and Dicloxacillin
What is amoxicillin the drug of choice for?
otitis media, can be combined with clavulanate (beta lactamase inhibitor)
What is ampicillin the drug of choice for?
Meningitis and other infections caused by Listeria monocytogenes. Often used with sulbactam (beta lactamase inhibitor)
What would you use as a surgical prophylaxis against staphylococci?
Cefazolin - 1st gen cephalosporin
What would you use to treat otitis media, when H. influenza is resistant to amoxicillin? What is this antibiotic also used to treat?
Cefprozil. Also treats community acquired pneumonia.
What are the drugs of choice for treating meningitis and gonorrhea caused by Neisseria?
Ceftriaxone (good for gonorrhea) or cefotaxime - 3rd gen cephalosporins
What is the mechanism of vancomycin?
A tricyclic glycopeptide that binds irreversibly to acyl-D-ala-D-ala terminus of peptidoglycan precursor. Inhibits crosslinking and membrane pore formation.
What is vancomycin used to treat?
- MRSA s. aureus. + other gram + bacteria
- patients allergic to penicillins
- enterococcal endocarditis
- psedumembraneous colitis caused by C. difficult
What are the adverse effects of vancomycin?
- infusion related toxicity
- red man syndrome due to histamine release
- ototoxicity at higher concentration
- enhances nephrotoxicity of amino glycosides and amphotericin B
What is the mechanism of amino glycosides?
They bind to 30S ribosomal subunit and interfere with initiation of protein synthesis. Cause misreading of genetic code, wrong amino acid is inserted into proteins. Results in post-antibiotic effect.
-synergistic with penicillins and vancomycin, which makes pores in bacterial cell wall for amino glycosides to enter.
What are adverse effects of aminoglycosides?
- Renal toxicity: most common cause of drug induced renal failure
- Ototoxicity: cochlear toxicity (irreversible) and vestibular toxicity
What is gentamicin used for? What class of antibiotics is it?
enterococcal and staphylococcal infection, viridans group strep infection (endocarditis). Aminoglycoside. not orally absorbed.
What is neomycin used for? What class of antibiotics is it?
Sometimes taken orally to treat hepatic coma and GI infections, for surgical prophylaxis in colorectal surgeries. Also used topically to treat skin infections (Neosporin).
What is the mechanism behind tetracyclines?
competitively block binding of tRNA to 30S subunit and prevent addition of new amino acids to growing peptide chain. Reversible.
What are the adverse effects of tetracyclines?
- epigastric distress-irritates gastric mucosa
- calcified tissues-bind to calcifying teeth and bones. Contraindicated in children under 8, pregnant women, and nursing mothers
- nephrotoxicity
- phototoxicity - sunburn
Describe the pharmacokinetics of tetracyclines.
- oral bioavailability reduced if ingested with products containing metals, e.g. dairy products, antacids, iron supplements
- mostly excreted in urine except doxycycline excreted in bile
What are the clinical uses of tetracyclines?
- Rickettsia infections -Rocky Mtn Spotted fever
- Lyme disease - Borrelia burgdorferi
- Mycoplasma pneumonia
- Chlamydia trachomatis
- Acne vulgaris
- Shorten chloera therapy
List two examples of tetracyclines.
Tetracycline and doxycycline
What is the mechanism behind macrolides?
- Bind to 50S subunit and prevent translocation of peptide from A site to P site
- Block peptidyl transferase, the enzyme that catalyzes formation of peptide bond between new amino acid and nascent peptide
- bacteriostatic
List two examples of macrolides.
Erythromycin and Azithromycin.
What are the adverse effects of macrolides?
- Epigastric distress (mainly erythromycin) - stimulates GI motility
- cholestatic jaundice - caused by hypersensitivity rxns
- ototoxicity
contraindications: not given to patients with hepatic dysfunction
Describe pharmacokinetics of macrolides?
- Don’t enter CSF
- Erythromycin and azithromycin excreted by bile
- diffuse into prostatic fluid
What are the clinical uses of macrolides?
- gram + mainly
- prophylaxis and treatment of pneumonia
- chlamydia trachomatis PID
- Otitis media of H. influenzae
- Peptic ulcer from H. pylori
What is the mechanism behind sulfonamides?
-inhibit dihydropteorate synthase and decrease levels of dihydrofolic acid in bacteria due to similarity to PABA
What is an example of a sulfonamide?
Sulfamethoxazole.
Describe the pharmacokinetics of sulfonamides.
- topical preparations
- inactivated by acetylation, excreted i urine
- may precipitate in renal tubules–>crystalluria because acetylated metabolites are less soluble
What are the drug interactions of sulfonamides?
- Displace other drugs such as methotrexate, warfarin, and sulfonylurea from albumin and increase their plasma conc. and toxicity.
- SMX (sulfamethoxazole) inhibits CYP and displaces warfarin from albumin–>increases plasma levels of warfarin
What are the adverse effects of sulfonamides?
- Skin rashes
- Stevens-Johnson syndrome- serious life threatening form
- Kernicterus in infants (sulfonamides displace bilirubin from albumin, bilirubin not eliminated well bc of insufficient glucuronosyl trnasferase in neonates)
What are sulfonamides used to treat?
- UTIs
- otitis media in kids (sulfisoxazole w/ erythromycin)
- skin infections and burn infections
What is the mechanism behind fluoroqinolones?
They inhibit DNA gyrase, results in breakdown of DNA.
What are examples of fluoroqinolones?
- ciprofloxacin
- levofloxacin
Describe the pharmacokinetics of fluoroquinolones?
- chelates metals, not taken with dairy or antacids
- long half lives
- long post antibiotic effect
- once a day oral administration
What are the adverse effects of fluoroquinolones?
- CNS problems with high doses of coffee
- phototoxicity
- arthropathy in children
What are the clinical uses of fluoroquinolones?
- broad spectrum
- UTI and prostatitis, including P aeruginosa and Enterobacteriaceae members
- diarrhea-campylobacter, salmonella, shigella, e. coli
- sinusitis, bronchitis due to pneumococci and H. influenzae
- pneumonia - levoflxacin
What are the drugs that are used to treat tuberculosis? Combination of 4 of five
Isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin
What is the mechanism of isoniazid?
Inhibits synthesis of my colic acids, essential to cell wall.
What is the mechanism of rifampin?
Binds to beta subunit of RNA polymerase and inhibits transcription.
What is the mechanism of ethambutol?
Blocks arabinosyl transferases involved in cell wall synthesis.
What are the adverse effects of isoniazid?
Hepatitis,, peripheral neuropathy (prevented by B6)
What are the adverse effects of rifampin?
Hepatitis
hypersensitivity reaction
discoloration of body fluids
What are the adverse effects of ethambutol?
optic neuritis (can't distinguish between red/green) acute gout
List the nitrogen mustards.
mechlorethamine and cyclophosphamide
List the nitrosoureas.
Carmustine
semustine
lomustine
streptozotocin
List the anticancer platinum compounds.
Cisplatin
carboplatin
List the anti cancer methylating agents.
procarbazine
What is mechlorethamine used to treat?
Part of Hodgkin’s MOPP regimen
Which anticancer alkylating agents are prodrugs?
Procarbazine and cyclophosphamide
What are the synthetic nitrosoureas used to treat?
brain tumors (primary metastases)
What is streptozotocin used to treat?
pancreatic islet cell carcinoma
Which platinum compound is preferred? (carboplatin or cisplatin) And why?
Cisplatin because it has low myelosuppression, though it has nephrotoxicity and ototoxicity. Carboplatin has high myelosuppression.
What should procarbazine not be taken with and why?
- tyramine containing foods such as cheese, yogurt, and wine. Causes hypertension because inhibition of MAO leads to elevations of tyramine and norephinephrine.
- antidepressants, potentiates sedative effects of phenothiazine, barbiturates, and narcotics (metabolized by Cytochrome P450)
What is an adverse effect of cyclophosphamide?
hemorrhagic cystitis
What is the mechanism of methotrexate?
- Methotrexate is a folic acid analog. It is a competitive inhibitor of dihydrofolate reductase Indirectly decreases synthesis of methyl donor for thymidylate synthase which catalyzes the production of DNA precursor dUMP->dTMP
- also inhibits de novo synthesis of purines at higher concentrations
- In tumor cells, additional glutamate residues are added and prevents exit of methotrexate from the cell, makes it a better inhibitor of DHFR
What can prevent the binding of methotrexate to dihydrofolate reductase and protect normal tissue?
Leucovorin-reduced folate analogue.
What drugs should be avoided while taking methotrexate?
Aspirin or sulfonamide. They displace methotrexate from albumin, inhibits its tubular secretion, and increases its levels in the plasma and its toxicity
List the pyrimidine antagonists.
5-fluorouracil and 5-fluorodeoxyuridine
What is the mechanism of action for 5-fluorouracil?
- prodrug–>FdUMP
- FdUMP inactivates thymidylate synthase
- analog of uracil
also
FU–>FUTP, incorporated into RNA leading to altered function and decreased protein synthesis
What is the mechanism of fluorodeoxyuridine?
single step reaction
converted into FdUMP to inhibit thymidylate synthase.
-inhibits DNA precursor synthesis.
-analog of deoxyuridine
What are the clinical functions of 5-fluorouracil and fluorodeoxyuridine?
Fluorouracil used in many cancers
Fluorodeoxyuridine only for intra arterial infusion of liver, head and neck tumors.
What are the purine antagonists? What are their analogs?
6-mercaptopurine - hypoxanthine analog
6-thioguanine - guanine analog
How do 6-mercaptopurine and 6-thioguanine work?
- prodrugs converted to thioucleotides
- HPRTase converts
mercaptopurine to thio-IMP
thioguanine to thio-GMP - They inhibit first committed step in purine pathway (amidophophoribosyl transferase) and branching point where IMP becomes AMP and GMP (IMP dehydrogenase)
- thio GMP–>thio GTP or thio-dGTP and incorporated in RNA or DNA
- thio IMP–>thio GMP and incorporated into nucleic acids
Summary: inhibits synthesis of purine precursors and incorporated into both RNA and DNA
How does drug resistance developed to thiopurines (6 mercaptopurine and 6 thioguanine?
- decreased HPRTase (activating enzyme)
- increased membrane bound alkaline phosphatase
What drug does 6-mercaptopurine interact with? How?
- allopurinol
- allopurinol decreases metabolic inactivation of 6-MP by inhibiting xanthine oxidase and prolongs half life of 6-MP and increases its toxicity
What are thiopurines used to treat?
acute leukemia, maintenance therapy for chronic granulocytic leukemia
How does cytarabine (cytosine arabinoside work?
- prodrug
- analog of deoxycytidine
- activated by doexycitidine kinase, incorporates into and terminates DNA chain elongation. Inhibits DNA polymerase at high concentrations
How does cancer resist cytarabine?
- decrease in drug activating enzyme deoxycitidine kinase, or low retention of are-CTP
- increase in drug inactivating enzymes, deoxycitidine deaminase or dCMP deaminase
What is cytarabine used for?
acute leukemia in children and adults. Not solid tumors.
What are the adverse effect of cytarabine?
high doses case seizures and cerebral dysfunction. Lack of deaminase activity in CNS, so more persistent in CSF
